HIV researchers have begun to focus on the difficult questions that require correlating cell culture and animal model findings with clinical observations. Recent studies have shown that HIV phenotype and the expression of so-called ancillary viral genes such as nef are likely to play important roles in HIV transmission and/or disease progression; that although the immune system appears to clear virus from the blood during acute infection, HIV seeds lymph tissue and replicates throughout disease, and that several alternative mechanisms, including superantigens, apoptosis, autoimmunity, increased viral replication leading to destruction of lymph tissue and others have been proposed to account for the gradual loss of immune function that is the hallmark of AIDS. There is an urgent need to better define the nature of transmitted viruses, the extent of viral genetic and serologic diversity, and the immune correlates of protection to aid in the design of effective vaccines. A better understanding of the mechanism(s) of disease pathogenesis and the mechanism of action of critical viral genes would yield valuable clues as to how we might be able to more effectively combat HIV replication, and preserve or restore immune function. This meeting will focus attention on several critical questions in HIV pathogenesis, what has been learned over the past year, and what focus is needed for the future to improve the base of knowledge on which to design and develop effective vaccines and therapeutic strategies.